Exploring amygdala structural changes and signaling pathways in postmortem brains: consequences of long-term methamphetamine addiction.

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

Assessment of prognostic biomarkers in sudden sensorineural hearing loss: A systematic review and meta-analysis.

Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in otolaryngology. Various biomarkers have been used to determine the prognosis of SSNHL. This systematic review and meta-analysis aims to evaluate the relationship between the different biomarkers and the prognosis of SSNHL. We searched English-language literature up to October 2022 in four databases, including PubMed, Google Scholar, Cochrane, and Science Direct. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study was reported in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID = CRD42022369538). All studies examining the role of neutrophil to lymphocyte ratio (NLR) concluded that higher NLR is associated with a worse prognosis. The results of studies regarding the relationship between platelet to lymphocyte ratio (PLR) and tumor necrosis factor (TNF) are controversial. Other factors shown to be associated with SSNHL include Glycated hemoglobin (HbA1C), blood glucose, iron levels, serum endocan, salusin-beta, and bone turnover biomarkers. This meta-analysis showed that PLR, NLR, and neutrophils were significantly different between recovered and non-recovered patients. PLR, NLR, and neutrophil count are reliable tools to assess the prognosis of patients with SSNHL.

Combined treatment of retinoic acid with olfactory ensheathing cells protect gentamicin-induced SGNs damage in the rat cochlea in vitro.

Hearing is mainly dependent on the function of hair cells (HCs) and spiral ganglion neurons (SGNs) which damage or loss of them leads to irreversible hearing loss. Olfactory ensheathing cells (OECs) are specialized glia that forms the fascicles of the olfactory nerve by surrounding the olfactory sensory axons. The OECs, as a regenerating part of the nervous system, play a supporting function in axonal regeneration and express a wide range of growth factors. In addition, retinoic acid (RA) enhances the proliferation and differentiation of these cells into the nerve. In the present study, we co-cultured human OECs (hOECs) with cochlear SGNs in order to determine whether hOECs and RA co-treatment can protect the repair process in gentamycin-induced SGNs damage in vitro. For this purpose, cochlear cultures were prepared from P4 Wistar rats, which were randomly appointed to four groups: normal cultivated SGNs (Control), gentamicin-lesioned SGNs culture (Gent), gentamicin-lesioned SGNs culture treated with OECs (Gent + OECs) and gentamicin-lesioned SGNs culture co-treated with OECs and RA (Gent + OEC& RA). The expression of a specific protein in SGNs was examined using immunohistochemical and Western blotting technique. TUNEl staining was used to detect cell apoptosis. Here, we revealed that combined treatment of OECs and RA protect synapsin and Tuj-1 expression in the lesioned SGNs and attenuate cell apoptosis. These findings suggest that RA co-treatment can enhance efficiency of OECs in repair of SGNs damage induced by ototoxic drug.

Photobiomodulation Therapy and Cell Therapy Improved Parkinson's Diseases by Neuro-regeneration and Tremor Inhibition.

Introduction: Parkinson's disease (PD) is a progressive and severe neurodegenerative disorder of the central nervous system (CNS). The most prominent features of this disease are cell reduction in the substantia nigra and accumulation of α-synuclein, especially in the brainstem, spinal cord, and cortical areas. In addition to drug-based treatment, other therapies such as surgery, cell therapy, and laser therapy can be considered. In this study, articles on cell therapy and laser therapy for PD have been collected to evaluate the improvement of motor function, cell differentiation, and dopaminergic cell proliferation. Methods: Articles were collected from four electronic databases: PubMed, Scopus, Google Scholar, and Web of Science from 2010 to 2022. The keywords were "photobiomodulation", "low-level light therapy", "Low-level laser therapy", "near-infrared light", "Parkinson's disease", "Parkinsonism", and "stem cell therapy". About 100 related articles were included in the study. Results: The results of the studies showed that cell therapy and laser therapy are useful in the treatment of PD, and despite their limitations, they can be useful in improving PD. Conclusion: Concomitant use of cell therapy and photobiomodulation therapy can improve the symptoms of PD.

Therapeutic Effects of Photobiomodulation Therapy on Multiple Sclerosis by Regulating the Inflammatory Process and Controlling Immune Cell Activity: A Novel Promising Treatment Target.

Introduction: Multiple sclerosis (MS) is one of the autoimmune and chronic diseases of the central nervous system; this disease occurs more frequently in young people and women and leads to neurological symptoms. Oxidative stress, inflammatory processes, and oligodendrocyte dysfunction have a pivotal role in the pathophysiology of this disease. Nowadays it is reported that photobiomodulation (PBM) as a non-invasive treatment has neuroprotective potential, but the exact mechanisms are not understood. Methods: In this study, we reviewed the effects of PBM on MS. In this regard, we used the keywords "Photobiomodulation", "Laser therapy", and "Low-level laser therapy" on MS to find related studies on this subject in PubMed, Google scholar, Elsevier, Medline, and Scopus databases. Results: PBM has positive effects on MS by regulating the inflammatory process, controlling immune cell activity and mitochondrial functions, as well as inhibiting free radicals production which finally leads to a reduction in neurological defects and an improvement in the functional status of patients. Conclusion: Overall, researchers have suggested the use of laser therapy in neurodegenerative diseases due to its numerous therapeutic effects.

Apelin-13 prevents apoptosis in the cochlear tissue of noise-exposed rat via Sirt-1 regulation.

Noise-induced hearing loss (NIHL) is the second most common cause of acquired hearing loss. Acoustic trauma can cause oxidative damage in the cochlear hair cells (HCs) through apoptotic pathways. Apelin is a newly discovered neuropeptide with neuroprotective effects against the oxidative stress in neurodegenerative disorder. We investigated the preventive effects of apelin-13 on the cochlear HCs and spiral ganglion neurons (SGNs) against acoustic trauma via Sirtuin-1 (Sirt-1) regulation in rats. Animals were assigned to control, control + apelin-13 (50 or 100 µg/kg, ip), and noise exposure groups without any treatment or were administered apelin-13 (50 or 100 µg/kg, ip) and EX-527 (an inhibitor of Sirt-1) prior to each noise session. In the noise groups, 110 dB white noise was applied for 6 h per 5 days. Pre- and post-exposure distortion product otoacoustic emissions (DPOAE) and cochlear superoxide dismutase (SOD) activity were assessed. Western blot evaluated the cochlear protein expressions of Sirt-1, cleaved-caspase-3, Bax, and Bcl-2. Cell apoptosis was detected through TUNEL staining. Immunofluorescence was used to examine expression of HCs and SGNs specific protein. DPOAE level were significantly improved in the noise exposure group receiving 100 µg/kg apelin-13. At high doses, apelin augmented SOD levels in the rat cochlea subjected to noise. Apelin 100 markedly increased Sirt-1, and decreased cleaved- caspase-3 expression as well as Bax/Bcl-2 ratio in the cochlea tissue of noise-exposed rats. These findings suggest the promising therapeutic potential of apelin-13 for the prevention of noise-induced injury to cochlea and hearing loss.

NUPR1- CHOP experssion, autophagosome formation and apoptosis in the postmortem striatum of chronic methamphetamine user.

Methamphetamine (Meth) is a neuro-stimulator substrate which might lead to neural cell death and the activation of several interconnected cellular pathways as well. However, the precise molecular mechanisms underlying Meth-induced neural cell death remained unclear yet. The current study aimed to assess the specific relationship between long-term Meth exposure and several endoplasmic reticulum stress, autophagy, and apoptosis associated markers including C/EBP homologous protein (CHOP), Tribbles homolog 3(Trib3), Nuclear protein 1(NUPR1), and Beclin-1 expression in postmortem human striatum. Therefore, the effects of long-term Meth exposure on autophagy and apoptosis in the striatum of postmortem users were evaluated and molecular, immunehistochemical, and histological examinations were performed on 10 control and 10 Meth-addicted brains. The level of CHOP, Trib3, NUPR1, and Beclin-1, Microtubule-associated proteins 1A/1B light chain 3B(LC3), Caspase 3, and Autophagy protein 5 (ATG5) were measured by using qPCR and immunohistochemistry. Stereological neural cell counting, Hematoxylin and Eosin, Nissl and Tunel staining were also performed. Based on our findings, the expression level of CHOP, Trib3, NUPR1, and Beclin-1 in the striatum of Meth group were significantly higher than the control group. Besides, the neuronal cell death was substantially increased in the striatum based on data obtained from the Tunel assay and the stereological analysis. Long-term presence of Meth in the brain can induce ER stress and overexpression of NUPR1 which is associated with the upregulation of CHOP, a pro-apoptotic transcription factor. Moreover, an increase in Trib3 expression is implicated in CHOP-dependent autophagic cell death during Meth-induced ER stress accompanied by an increase in neuronal cell death in the striatum of the postmortem human brains. Beclin 1 expression was also upregulated which may due to the activation of autophagic mechanisms upon prolonged Meth exposure.

Therapeutics effects of [Pyr1] apelin-13 on rat contusion model of spinal cord injury: An experimental study.

Spinal cord injury (SCI) can cause various symptoms, including pain, complete or incomplete loss of autonomic, sensory, motor and functions inferior to the site of the damage. Despite wondrous advances in medicine, treating spinal cord injuries remains a thorny issue yet. Recently, the control of inflammatory processes after damage to the nervous system has been noticed as a promising therapeutic target. The goal of the present experiment was to identify the effects of apelin-13 on the histological outcome, inflammatory factors, and functional recovery in the animal contusion model of SCI were analyzed. 40 Female Wistar rats were randomly but equally assigned in laminectomy, contusion, PBS (1 mL PBS, i.p), control group which received apelin-13 (control + apelin, 100 µg/kg, i.p), and apelin-13 treatment groups. In the treatment group, apelin-13 (100 µg/kg) was injected intraperitoneally 30 min after injury. The weight-dropping contusion model was used for inducing SCI. The Basso, Beattie, and Bresnahan scale (BBB), narrow beam test (NBT), rotarod test, and the open-field test was applied to evaluate locomotor and behavioral activity. Real-time polymerase chain reaction (PCR) and ELISA technique was accomplished eight weeks after inducing SCI to measure the level of fibroblast growth factor FGF-1, FGFR1 and the inflammatory factors including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-6, and IL-10. Furthermore, histological change was estimated by H&E staining. Our results showed that apelin-13 treatment after SCI led to a significant increase in functional recovery and behavioral tests. Stereological estimation illustrated that apelin-13 could reduce significantly central cavity volume and number of glial cells, and also increase significantly spinal cord volume and number of neural cells. PCR and ELISA evaluation shows a significant increase in IL-10 level and decrease in levels of FGF-1, FGF-R1, and pro-inflammatory cytokines (PIC). This study suggested that apelin-13 has neuroprotective effects by regulating the inflammatory process after SCI.

Elevated Blood-Based Brain Biomarker Levels in Patients with Epileptic Seizures: A Systematic Review and Meta-analysis.

Recently, growing attention has been paid to the changes of brain biomarkers following the epilepsy. However, establishing specific epilepsy-related biomarkers has been impeded due to contradictory findings. This study systematically reviewed the evidence on brain biomarkers in epilepsy and determined reliable biomarkers in epileptic patients. A comprehensive systematic search of online databases was performed to find eligible studies up to August 2019. The quality of studies methodologically was assessed using the Newcastle-Ottawa Scale score. Among the several biomarkers, S100 calcium binding protein B (S100B) and neuron specific enolase (NSE) have been qualified for meta-analysis of the association between epilepsy and the brain biomarkers. Inverse-variance weights method was used to calculate pooled standardized mean difference (SMD) estimate with 95% CI, and random effects meta-analysis was conducted taking into account conceptual heterogeneity. Sensitivity analysis and publication bias assessment was performed using Stata. Of 29 studies that were qualified for further analysis, only 22 studies were eligible to quantify by meta-analysis. Significant increase of serum S100B levels (SMD = 0.80; 95% CI 0.18 to 1.42) but not NSE (SMD = 0.45; 95% CI -0.09 to 1.00) has been found in epileptic patients compared with healthy controls. Subgroup meta-analysis by age demonstrated that S100B could be found in pediatric (SMD = 1.15; 95% CI 0.03 to 2.27) not adult patients (SMD = 0.43; 95% CI -0.12 to 0.98). Findings of this meta-analysis indicate that serum level of S100B is significantly increased in epileptic patients, suggesting the elevation and release of the brain biomarkers from brain to blood following epileptic seizures.

LC3 and ATG5 overexpression and neuronal cell death in the prefrontal cortex of postmortem chronic methamphetamine users.

Methamphetamine (METH) abuse is accompanied by oxidative stress, METH-induced neurotoxicity, and apoptosis. Oxidative stress has devastating effects on the structure of proteins and cells. Autophagy is an evolutionarily conserved intracellular regulated mechanism for orderly degradation of dysfunctional proteins or removing damaged organelles. The precise role of autophagy in oxidative stress-induced apoptosis of dopaminergic neuronal cells caused by METH has not clarified completely. In this study, we sought to evaluate the effects of METH abuse on autophagy in the prefrontal cortex of postmortem users, mainly focusing on the ATG5 and LC3 during neuroinflammation. Postmortem molecular and histological examination was done for two groups containing 12 non-addicted and 14 METH addicted cases. ATG5 and LC3 expression were analyzed by real-time PCR and immunohistochemistry (IHC) methods. Histopathological analysis was performed by stereological cell counting of neuronal cells using Hematoxylin and Eosin (H & E) staining technique. In order to detect DNA damage in the prefrontal lobe, Tunnel staining was performed. Real-time PCR and IHC assay showed overexpression of ATG5 and LC3 protein in the prefrontal cortex of Meth users. The cell death and neuronal degeneration were increased significantly based on Tunel assay and the stereological analysis in the Prefrontal cortex. Chronic METH exposure probably induces ATG5 and LC3 overexpression and neuronal cell death in the Prefrontal cortex of the postmortem cases.

Carvacrol reduces hippocampal cell death and improves learning and memory deficits following lead-induced neurotoxicity via antioxidant activity.

Carvacrol is a monoterpene with neuroprotective effects in several animal models of neurodegeneration, including epilepsy, ischemia, and traumatic neuronal events. In this study, we aimed to examine the effects of carvacrol on neurodegeneration induced by lead acetate in rats. A total of 50 male Wistar rats were divided into five equal groups. The control group received drinking water, while the neurotoxic group was exposed to 500 ppm of lead acetate in drinking water for 40 days. The three remaining groups, which were also exposed to 500 ppm of lead acetate, received carvacrol at doses of 25, 50, and 100 mg/kg orally for 40 days. The Morris water maze test was employed to examine spatial learning and memory. Pathological damage to the hippocampus was determined by Nissl staining. The level of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were detected using biochemical analysis and the free radical scavenging activity as evaluated by the DPPH test. Administration of carvacrol significantly restored learning and memory impairment induced by lead acetate. Moreover, carvacrol ameliorated neurodegeneration, antioxidative capacity, and lipid peroxidation in the hippocampus of rats exposed to lead. The present results provide a rationale for the inhibitory role of carvacrol in the attenuation of lead-induced neurotoxicity.

Protective effect of [Pyr1]-apelin-13 on oxidative stress-induced apoptosis in hair cell-like cells derived from bone marrow mesenchymal stem cells.

Oxidative stress plays an important role in auditory dysfunction. Exogenous cell therapy has brought new hopes for repairing mammalian inner ear hair cells. However, poor cell viability of transplanted cells under oxidative stress conditions has limited their therapeutic potential. The adipocytokine apelin-13 was isolated from a bovine stomach. Apelin-13 might protect oxidative stress-induced hair cell damage was raised considering other oxidative stress-induced injury, including brain ischemia-induced cell death. Therefore, we evaluated the protective effects of apelin- 13 on the damage induced by hydrogen peroxide (H2O2) to the hair cells-derived from bone marrow mesenchymal stem cells (BMSCs) in vitro. Stem cells were differentiated into hair cell- like cells with B27, FGF, EGF and IGF-1. Expression of neuron specific markers including ß tubulin III, Nestin, MAP2, Neurofilament 68 and GFAP was tested by flow cytometry. As well, inner ear hair cell markers such as Myosin VIIA, Sox2 and TrkB expression were assayed by immunocytochemistry (ICC) method. We designed an in vitro model of oxidative stress by exposing hair cell- like cells to H2O2. Protein expression levels of caspase-3, Bax and Bcl-2 were detected by western blot. Apoptotic cells were also detected by acridin-orange staining and TUNEL assay. Protein expression of caspase-3 and Bax/Bcl-2 ratio was significantly lower in the apelin-13-pretreated group than only H2O2 treated group. In addition, apoptotic cells were significantly decreased in the apelin-13+H2O2 co-treated cells compared to the H2O2-treated group. Treating hair cells-like cells with apelin13 increases their survival against oxidative stress damage by inhibition of apoptosis signaling pathway.

Postmortem Study of Molecular and Histological Changes in the CA1 Hippocampal Region of Chronic Methamphetamine User.

Methamphetamine (Meth) is recognized as one of the most important new distributed abused drug that causes severe damage to the different parts of the brain, especially hippocampus. Previous studies have demonstrated that Meth can induce apoptosis and cell death in the brain. In this study, we evaluated the long-term effects of Meth abuse in the CA1 region of postmortem hippocampus. Postmortem molecular and histological analysis was performed for five non-addicted subjects and five Meth addicted ones. Iba-1 (microglia) and glial fibrillary acidic protein, GFAP (astrocytes) expression were assayed by western blotting and immunohistochemistry (IHC) methods. Histopathological assessment was done with stereological counts of hippocampal cells stained with hematoxylin and eosin (H and E). Tunel staining was used to detect DNA damage in human brains. In addition, protein-protein interaction analysis network was investigated. Western blotting and immunohistochemistry assay showed overexpression of GFAP and Iba-1 protein in the CA1 hippocampal region of Meth users' brain. Stereological analysis in the CA1 region revealed increased neuron degeneration. Furthermore, significant apoptosis and cell death were confirmed by Tunel assay in the hippocampus. The prominent role of TLR4, IL1B, CASP1, and NLRP3 in the molecular mechanism of Meth was highlighted via PPI network analysis. Chronic Meth use can induce GFAP and Iba-1 upregulation and neuronal apoptosis in the CA1 region of the postmortem hippocampus.

Stem cell transplantation and functional recovery after spinal cord injury: a systematic review and meta-analysis.

Spinal cord injury is a significant cause of motor dysfunctions. There is no definite cure for it, and most of the therapeutic modalities are only symptomatic treatment. In this systematic review and meta-analysis, the effectiveness of stem cell therapy in the treatment of the spinal cord injuries in animal models was studied and evaluated. A systematic search through medical databases by using appropriate keywords was conducted. The relevant reports were reviewed in order to find out cases in which inclusion and exclusion criteria had been fulfilled. Finally, 89 articles have been considered, from which 28 had sufficient data for performing statistical analyses. The findings showed a significant improvement in motor functions after cell therapy. The outcome was strongly related to the number of transplanted cells, site of injury, chronicity of the injury, type of the damage, and the induction of immune-suppression. According to our data, improvements in functional recovery after stem cell therapy in the treatment of spinal cord injury in animal models was noticeable, but its outcome is strongly related to the site of injury, number of transplanted cells, and type of transplanted cells.

Axonal transport proteins and depressive like behavior, following Chronic Unpredictable Mild Stress in male rat.

BACKGROUND: A common mood disorder, depression has long been considered a leading cause of disability worldwide. Chronic stress is involved in the development of various psychiatric diseases including major depressive disorder. Stress can induce depressive-like symptoms and initiate neurodegenerative processes in the brain. The neurodegenerative theory of depression holds impaired axonal transport as a negative factor in neural survival. Axonal transport is a critical mechanism for normal neuronal function, playing crucial roles in axon growth, neurotransmitter secretion, normal mitochondrial function and neural survival. METHODS AND MATERIALS: To investigate the effects of stress-induced depression, in the present study, we evaluated behavior by forced swimming test (FST), corticosterone plasma level by ELISA assay, hippocampal mRNA expression of three genes (NGF, kinesin and dynein) via real-time PCR and hippocamp count by Nissl staining in male Wistar rats. RESULTS: Our data demonstrated a significant decrease in the expression of NGF, kinesin and dynein genes in CUMS groups compared to the control group (non-stressed) (p < 0.05). CUMS also caused an elevation in immobility time and corticosterone plasma level in the stressed group compared to the controls (p < 0.01 and p < 0.05, respectively). CONCLUSION: The results suggested that the possibility of stress-induced depressive behavior associated with hippocampal neurodegeneration process is correlated with a low expression of kinesin and dynein, the two most important proteins in axonal transport.

Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the deafened rat cochlea after acoustic trauma.

Previous animal studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling pathway plays an important role in the targeted migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the injured area. In the present study, we aimed to investigate the potential role of chemotactic SDF-1/CXCR4 signaling pathway in the homing of transplanted BMSCs to the injured cochlea after noise-induced hearing loss (NIHL) in a rat model. White noise exposure (110 dB) paradigm was used for hearing loss induction in male rats for 6 hours in 5 days. Distortion-product otoacoustic emission (DPOAE) responses were recorded before the experiment and post noise exposure. Hoechst 33342-labeled BMSCs and CXCR4 antagonist (AMD3100)-treated BMSCs were injected into the rat cochlea through the round window. SDF-1 protein expression in the cochlear tissue was assayed using western blot assay. The number of labeled BMSCs reaching the endolymph was determined after 24 hours. SDF-1 was significantly increased in the cochlear tissue of rats in the noise exposure group than in the control group. The number of Hoechst 33342-labeled BMSCs reaching the endolymph of the cochlea was significantly smaller in the AMD3100-treated BMSCs group than in the normal BMSCs group. Our present findings suggest that the SDF-1/CXCR4 signaling pathway has a critical role in BMSCs migration to the injured cochlea in a rat model of noise-induced hearing loss.

Neuroprotective effect of berberine chloride on cognitive impairment and hippocampal damage in experimental model of vascular dementia.

OBJECTIVES: The major objective of the present study was to investigate the potential neuroprotective effect of berberine chloride on vascular dementia. Berberine, as an ancient medicine in China and India, is the main active component derived from the Berberis sp. Several studies have revealed the beneficial effects of berberine in various neurodegenerative disorders. MATERIALS AND METHODS: To induce vascular dementia, chronic bilateral common carotid artery occlusion was performed on male Wistar rats. After surgery, the rats were treated daily by oral administration of berberine chloride (50 mg/kg) for two months. The cognition function of treated rats, were evaluated by Morris Water Maze (MWM) test. In addition, Nissl and TUNEL staining were chosen to assess neuronal damage within the hippocampal CA1 area. RESULTS: It was obvious that chronic cerebral hypoperfusion (CCH), caused cognitive impairment and neuronal damages within CA1 hippocampal subregion. Berberine chloride was able to prevent cognitive deficits, (P<0.05) and reversed CCH-induced hippocampal neuronal loss and apoptosis, (P<0.05). CONCLUSION: Berberine chloride may be considered as a potential treatment for cognitive deficits and neuronal injury caused by CCH in the hippocampal CA1 area.

Hippocampal NR3C1 DNA methylation can mediate part of preconception paternal stress effects in rat offspring.

Many studies have been shown that maternal stress during pregnancy and in early life period influences offspring in the behavioral and molecular aspects in human and animal models. Recent research has indicated that the environmental condition of males before conception has effects on next generations. We evaluated whether preconception paternal stress (PPS) could influence on hippocampal glucocorticoid receptor gene (GR), (NR3C1) expression, corticosterone response and behavioral outcomes of their offspring. For this purpose, adult male rats were subjected to daily 10min session of forced swimming for 21 consecutive days. Then, two parental breeding groups were formed: stressed father (SF) and non-stressed father (NSF) or control group. 30-day-old pups were tested for anxiety-like behavior by using the elevated plus maze (EPM). Serum corticosterone level was also measured by ELISA. Hippocampal NR3C1 DNA methylation, gene and protein expression were respectively assayed by methylation sensitive restriction enzymes (Real Time PCR), Reverse Transcriptase PCR (RT-PCR) and Western-blotting in all groups. More anxiety-related behavior, serum corticosterone concentration, DNA methylation levels of NR3C1 and lower expression of this gene were significantly observed in paternally stressed pups compared to control pups. As well, molecular changes were more pronounced in male pups compared to female pups. Our results revealed that paternal stress prior to conception has a negative effect on molecular, hormonal and behavioral outcomes in their offspring.

Effect of Maternal Stress Prior to Conception on Hippocampal BDNF Signaling in Rat Offspring.

Environmental factors, especially stress, can remain pervasive effects across the lifespan. Traumatic experiences are risk factors for the behavioral and emotional disorders. Since brain-derived neurotrophic factor (BDNF) is the important regulator of neural survival, development, and its genetic and epigenetic alterations which have been linked with several neuropsychiatric disorders, the present study investigated the effect of maternal adulthood stress on molecular changes of BDNF and tyrosine kinase-coupled receptor (TrkB) in the hippocampus of 30-day-old offspring. To induce stress, we employed a repeated forced swimming model for female rats across 21 days. Then, they were divided into two parental breeding groups: stressed mother (SM) and non-stressed mother (NSM) or control group. Anxiety-like behavior was tested in adult female rats and 30-day-old pups by using the elevated plus maze (EPM). The level of serum corticosterone was also measured by ELISA. BDNF and TrkB gene methylation and protein expression in the hippocampus were detected using real-time PCR and Western blotting in all groups. Thirty-day-old male and female pups from SM groups had a significantly more serum corticosterone concentration, DNA methylation levels of BDNF and TrKB, and lower expression of these genes compared to pups from the control groups. Also, male pups from stressed mother exhibited significant anxiety-like behavior compared to male pups from the control mothers. These findings suggest that molecular changes formed by maternal stress experience even before conception persist to the next generation and will negatively influence on phenotypes of offspring.

The role of erythropoietin in remote renal preconditioning on hippocampus ischemia/reperfusion injury.

Remote ischemic preconditioning (RIPC) is an intriguing approach which exposes a remote organ/tissue to a non-lethal transient ischemia/reperfusion (I/R) in order to potentiate the resistance of the desired organ/tissue against the next unwanted I/R. It has been suggested that RIPC exerts its effect through neuronal and hormonal pathways. The underlying mechanisms of RIPC are obscure and should be elucidated. In this study, we induced RIPC in mice using 3 cycles of 5 min ischemia alternating with 5 min reperfusion of the left renal artery. Renal failure was induced in mice by intra-peritoneal (i.p.) injection of 200 mg/kg body weight of gentamicin twice per day for 4 consecutive days. Global hippocampal ischemia reperfusion (I/R) was performed by bilateral carotid artery occlusion for 20 min followed by reperfusion for 72 h. Moreover, the retention trial of passive avoidance test was determined 72 h after global ischemia. Histopathological changes of hippocampus neurons were observed using Nissl staining to detect neuronal loss. Finally, terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) was performed to assess the status of apoptotic cells in the hippocampus. The results of this study suggest that renal ischemic preconditioning is a good candidate for prevention of I/R-induced hippocampal injury. However, RRPC (remote renal preconditioning) failed to exert a neuroprotective effect in mice with renal failure (RF), indicating the probable role of a humoral factor which is released from kidneys in response to ischemia. In agreement with this hypothesis, treatment of mice with rhEPO (5000 IU/kg intraperitoneal) before induction of RRPC restored the neuroprotective effects of RRPC in RF mice. Accordingly, it is plausible to expect that erythropoietin is released from kidneys to act as a mediator for RRPC-induced neuroprotective effects. Renal ischemic preconditioning prevents I/R-induced hippocampal injury. In contrast, renal failure hampers protective effects of RRPC, while exogenous administration of erythropoietin (EPO) significantly prevents the inhibiting effects of renal failure.